{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T15:02:29Z","timestamp":1785078149152,"version":"3.55.0"},"reference-count":12,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Infantile\u2010onset cardiomyopathy due to mitochondrial dysfunction is a severe condition frequently associated with poor prognosis. Biallelic pathogenic variants in\n ELAC2<\/jats:italic>\n , an essential mitochondrial tRNA processing gene, have been implicated in this phenotype. This study investigates the clinical and genetic spectrum of\n ELAC2<\/jats:italic>\n \u2010related disease in a national cohort from Kuwait.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a retrospective cohort study using data from the Kuwait Medical Genetics Center registry, including individuals with genetically confirmed or clinically suspected\n ELAC2<\/jats:italic>\n \u2010related cardiomyopathy. Clinical, metabolic, and molecular data were reviewed. Exome sequencing or targeted mutation testing was performed in affected individuals and at\u2010risk family members.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 34 individuals from 23 consanguineous families were identified, of whom 30 were genetically confirmed to harbor the homozygous\n ELAC2<\/jats:italic>\n founder variant c.460T>C; p.(Phe154Leu). All individuals presented in infancy with severe cardiomyopathy and refractory lactic acidosis. Neurological involvement was observed in 39% of cases. The majority exhibited hypertrophic cardiomyopathy, with variable dilated features and pericardial effusion. The disease course was fatal in all, with most patients dying in infancy.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This is the largest single\u2010country cohort reported to date with\n ELAC2<\/jats:italic>\n \u2010related mitochondrial cardiomyopathy, raising the global case total to over 70. The uniform presence of the\n Phe154Leu<\/jats:italic>\n variant across unrelated Bedouin families highlights a strong founder effect. Given the rapid disease progression and high mortality, we recommend targeted\n ELAC2<\/jats:italic>\n screening in infants with idiopathic cardiomyopathy and persistent lactic acidosis, particularly in consanguineous populations. Premarital carrier testing and early family counseling should be prioritized to support preventive strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70274","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:54:11Z","timestamp":1784606051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Homozygous Founder\n \n ELAC2<\/i>\n <\/scp>\n Variant in Kuwaiti Infants With Fatal Cardiomyopathy and Refractory Severe Lactic Acidosis: A Retrospective Review of the Clinical, Cardiological and Molecular Findings"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-0311","authenticated-orcid":false,"given":"Hind","family":"Alsharhan","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Health Sciences Centre, College of Medicine Kuwait University Safat Kuwait"},{"name":"Kuwait Medical Genetics Center, Ministry of Health Sulaibikhat Kuwait"},{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Worood","family":"Alostad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jaber Al\u2010Ahmad Hospital Ministry of Health Kuwait Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3283-7800","authenticated-orcid":false,"given":"Alshaymaa A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"},{"name":"Department of Pediatrics, Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5503-5193","authenticated-orcid":false,"given":"Mohammad A.","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Health Sciences Centre, College of Medicine Kuwait University Safat Kuwait"},{"name":"Cardiology Department, Chest Hospital Ministry of Health Kuwait Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4039-0758","authenticated-orcid":false,"given":"Hesham A. F.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-2532","authenticated-orcid":false,"given":"Ahmad","family":"Alahmad","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center, Ministry of Health Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hashem","family":"Alhashemi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9369-2493","authenticated-orcid":false,"given":"Walid M.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad E. M. S.","family":"Alhaj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Farwaniya Hospital Ministry of Health Sabah Al\u2010Nasser Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha M.","family":"Alsafi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Adan Hospital Ministry of Health Hadiya Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9695-3231","authenticated-orcid":false,"given":"Buthaina","family":"Albash","sequence":"additional","affiliation":[{"name":"Kuwait Medical Genetics Center, Ministry of Health Sulaibikhat Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010016\u20100526\u20108"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13020445"},{"key":"e_1_2_12_4_1","unstructured":"Children's Cardiomyopathy Foundation.2025.\u201cCCF\u2013About the Disease\/Causes.\u201dCited on June 8 2025. Accessed 8 June 2025.https:\/\/www.childrenscardiomyopathy.org\/pages\/about\u2010disease\/causes\/."},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.006"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3345\/KJP.2017.60.12.408"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2217\/FCA.13.62"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.YMGME.2016.04.009"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006320"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960\u20108966(01)00248\u20106"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23777"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000465516"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/JAMA.2014.7184"}],"container-title":["Molecular Genetics & Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70274","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.70274","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T14:50:31Z","timestamp":1785077431000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mgg3.70274"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70274","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-09-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70274"}}